Oral 13-cis-retinoic acid was effective in the treatment of skin cancer, and a variety of disorders of keratinization (lamellar ichthyosis, Darier's disease, pityriasis rubra pilaris), and cystic acne. An oral synthetic aromatic derivative of retinoic acid (RO-10-9359) was more effective and less toxic than 13-cis-retinoic acid in the treatment of the disorders of keratinization. A high initial followed by a low maintenance dosage of 13-cis-retinoic acid was comparably effective but less toxic than previously used continuous high-dosage schedules in the treatment of cystic acne. The high-low dosage schedule was superior to the high initial dose schedule used alone and to a continuous low dose schedule. 13-cis-retinoic acid led to small but significant elevations in plasma lipids and changes in lipoproteins during therapy. RO-10-9359 produced similar changes which were dose dependent and responsive to dietary management. Absorption of RO-10-9359 is greater with milk than with water. Etretinate is bound in plasma to beta-liproproteins. Administration of etretinate with milk vs. water yielded different ratios of drug to metabolite in the serum. One chronic toxicity, "Retinoid Hyperostosis" has been observed with long-term, high-dose isotretinoin: Anterior spinal ligament calcification and osteophyte formation of vertebrae.